Ginkgo Fails to Improve Cognitive Function in People with MS
Results of a 12-week clinical trial showed that Ginkgo Biloba failed to improve cognitive function in people with MS. The study involved 121 people with all types of MS whose cognitive tests showed some cognitive impairment. After 12 weeks, no differences were seen between those on Ginkgo Biloba and those taking placebo in any of the outcome measures. The authors note that this study was not designed to determine the long-term impact of Ginkgo Biloba, and that the participants had had MS for a long duration (a median of 20 years), which may have influenced outcomes.
Personalized Medicine for Prognosis and Treatment of MS
What if we could predict the future?
One of the most frustrating aspects of treating multiple sclerosis, for both patients and doctors, is not knowing how an individual will respond to a particular medication. Our front line disease-modifying treatments, the ones we use first in treating someone with multiple sclerosis, all have demonstrable benefit in clinical trials and in real practice. However, not everyone’s MS responds equally to all of these medications. This variance exists strictly in terms of effectiveness of the medication, without considering tolerance for temporary side effects or preferences for frequency of administering the drugs.
Strictly in terms of the success of the drug in reducing relapses and lessening severity of attacks (assuming adherence), some patients do well with the first therapy they’re given. Others don’t, and after months or years on a particular drug, doctor and patient make the decision to switch therapies. The waiting period then begins anew to see if the patient’s MS will respond with fewer and less severe relapses. This can be very troubling emotionally because the disease and symptoms can continue to progress as time passes. Most patients with Relapsing-Remitting MS eventually find a therapy that works for their MS; however, there are some who don’t.
No doctor can predict which patients will respond best to which drugs. However, if a doctor could identify which patients were more likely to respond to treatment, and if there were clues as to how active their disease will be, it would give doctors a tremendous advantage in recommending therapy. MS research now seems to be on the path to do precisely that at some point not too long from now.
A team led by Philip L. De Jager, MD, a Harry Weaver Scholar of the National MS Society, who is affiliated with Harvard Medical School and Brigham and Women’s Hospital in Boston, has discovered that differences in active genes–detectable in blood samples–has the potential to be used to group people with MS into categories that predict disease course and response to therapy. Of course, further research is needed to verify and refine this approach before it becomes a tool that can benefit treatment decisions made by people with MS and their health care providers. This study was recently published in Science Translational Medicine [4, 153ra131 (2012)].
The De Jager team looked for clues about gene activity in MS disease patterns by determining which genes are active or inactive in patient blood samples. They related specific disease patterns to the genes that were turned on or off in the patient samples. Blood samples from 141 people who were newly diagnosed with MS and who had not yet been treated were examined. The blood samples contain immune cells known to be important in the disease activity involved in MS. From these cells, the team extracted a type of molecule called RNA, which shows what genes are turned on in the immune cells. They used powerful mathematical tools to study the many groups of genes that were switched on.
This analysis showed that the 141 people with MS could be divided into two groups according to whether particular sets of genes involved in immune function were active or inactive. They then tested the importance of their groupings further by examining blood from 222 people who were being treated with two types of first-line therapy used in MS. The group of people with MS whose immune system genes were more active were significantly more likely to experience a relapse or show other evidence of disease activity, such as on MRI, were compared to the group whose immune system genes were less active, regardless of which treatment they were on. In this way, the team was able to find a “signature” by looking at the blood that could predict, early on at least, the likelihood of active disease.
It’s very important to note that there is much that this study doesn’t tell us, because it was a first step, and there are many more questions to answer, including whether this process can predict a shift from a relapsing form of MS to a progressive state. But it is extremely promising, and could eventually contribute towards “personalized medicine” in MS, which aims to be able to predict the course of an individual’s disease and the best treatment options to stop their type of disease activity.
In a disease as complicated as MS, this provides great hope to both doctors and patients as they work together to overcome multiple sclerosis. It is also an excellent example of the growing power of MS research to employ genetic data in a treatment context. To learn more about Dr. DeJager’s work, visit www.nationalMSsociety.org/research and select “Stopping the disease.”
Understanding Clinical Trials
People with multiple sclerosis who participate in clinical trials help make new and better therapies possible. The National MS Society has updated information about ongoing clinical trials for MS at www.nationalMSsociety.org/2012trials. There, you can download PDFs on the following specific types of clinical trials:
- Trials funded by the National MS Society
- Large phase III trials in relapsing-remitting MS
- Trials in progressive forms of MS
- Trials of symptomatic treatments
The U.S. Food and Drug Administration (FDA) requires therapies to undergo three phases of clinical trials before they can be approved to treat people with MS.
- Phase I: The first step is to determine safety. In a small number of healthy volunteers or people with MS, researchers investigate how the body reacts to a therapy.
- Phase II: If the therapy proves to be safe, studies begin to determine a drug’s effectiveness in people with MS. These studies may last several months or several years, and involve larger numbers of people. The study is “controlled” - that is, the drug is compared with the standard treatment or a placebo.
- Phase III: If an MS drug shows effectiveness, an even larger study is conducted in hundreds of people to gain a better understanding of the drugs’s effectiveness and possible side effects.
- Phase IV: These are not required for FDA approval, but might be conducted afterward to assess long-term safety and effectiveness.
For more on clinical trials, visit the clinical trials registry created by the National Institutes of Health at www.clinicaltrials.gov.
Society Collaborates with International Partners to Speed Progressive MS Research
The newly formed International Collaborative on Progressive MS recently published an opinion paper identifying key research priorities to propel efforts to stop MS progression. The Collaborative commissioned five working groups to identify strategies and potential lines of research within each area.
Investigators Recruiting for Personalized T Cell Immunotherapy Study in Secondary-Progressive MS
Investigators are recruiting people with secondary-progressive MS for a study to determine the effectiveness of Tcelna™ (imilecleucel-T, Opexa Therapeutics) in slowing disease progression in this progressive population. The study, known as the Abili-T study, is sponsored by Opexa Therapeutics, Inc.
Tcelna (imilecleucel-T) is a personalized T-cell product that aims to induce immunity against T cells that attack the brain and spinal cord in MS. It uses a person’s own immune cells, which are removed from the blood, expanded in culture, and reintroduced by under the skin injections. It is designed to restore deficient regulatory T-cell function in individuals with MS. The primary purpose of this study is to determine whether imilecleucel-T (given in five doses annually over two years) can restore immune function, alleviate chronic inflammation and reduce neurodegeneration that drives clinical progression in people with Secondary-Progressive MS.
Research shows that production of the anti-inflammatory immune messenger protein, IL-10, by regulatory T-cells is deficient in individuals with secondary-progressive MS, when compared to either people without MS or those with relapsing-remitting MS. This study examines whether an experimental treatment that may increase IL-10 production will decrease disability progression and decrease the rate of brain volume loss (atrophy) on MRI scans.
To learn more about this study, and to find out if you are eligible to participate, please visit the study listing on clinicaltrials.gov and contact the site nearest you: http://clinicaltrials.gov/ct2/show/NCT01684761. Local sites will be enrolling in Boston, MA and Burlington, VT.
EDITOR’S NOTE: A story that ran in the last newsletter, titled “New Findings at AAN Meeting” described results of a phase III trial that compared intravenous alemtuzumab against standard dosing of Rebif (interferon beta-1a). The story reported that the relapse rate in 840 people with relapsing-remitting MS was reduced by 49 percent and the risk of disability progression reduced by 42 percent. However, it omitted the fact that more severe adverse events were reported in those on alemtuzumab. These included autoimmune thyroid-related problems in 15.9%, ITP (a rare blood disorder) in 0.9%, and infusion-related reactions. Serious infections occurred in 3.7% of the alemtuzumab group and 1.5% of the Rebif group.